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Molecular and Cellular Biology, December 2007, p. 8318-8329, Vol. 27, No. 23
0270-7306/07/$08.00+0     doi:10.1128/MCB.01209-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functional Roles of Otx2 Transcription Factor in Postnatal Mouse Retinal Development{triangledown} ,{dagger}

Chieko Koike,1,{ddagger} Akihiro Nishida,1,{ddagger} Shinji Ueno,5 Hiromitsu Saito,4 Rikako Sanuki,1 Shigeru Sato,1,2 Akiko Furukawa,1 Shinichi Aizawa,3 Isao Matsuo,3 Noboru Suzuki,4 Mineo Kondo,5 and Takahisa Furukawa1*

Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan,1 Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan,2 Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan,3 Department of Animal Genomics, Functional Genomics Institute, Mie University Life Science Research Center, 2-174 Edobashi, Tsu, Mie 514-8507, Japan,4 Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan5

Received 8 July 2007/ Returned for modification 29 August 2007/ Accepted 17 September 2007

We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2+/–; Crx–/– retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx–/– retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2+/–; Crx–/– retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cell-specific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells.

* Corresponding author. Mailing address: Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan. Phone: 81-6-6872-4853. Fax: 81-6-6872-3933. E-mail: furukawa{at}obi.or.jp

{triangledown} Published ahead of print on 1 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} C.K. and A.N. equally contributed to this work.

Molecular and Cellular Biology, December 2007, p. 8318-8329, Vol. 27, No. 23
0270-7306/07/$08.00+0     doi:10.1128/MCB.01209-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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